Immunotherapy Before and After Surgery for Treatment of Recurrent or Progressive High Grade Glioma in Children and Young Adults

Glioblastoma Clinical Trial

Official title: A Single Arm, Pilot of Neoadjuvant Checkpoint Inhibition Followed by Adjuvant Checkpoint Inhibition in Children and Young Adults With Recurrent or Progressive High Grade Glioma (HGG)

Status Recruiting

Clinical Trial Summary

This phase I trial studies the side effects of nivolumab before and after surgery in treating children and young adults with high grade glioma that has come back (recurrent) or is increasing in scope or severity (progressive). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To measure the relative changes in cell cycle-related genetic signature of the tumor microenvironment post administration of neoadjuvant nivolumab in children and young adults with recurrent or progressive HGG when compared to a cohort of archived non-treated recurrent pediatric HGG samples.

II. To characterize the safety and tolerability of neoadjuvant nivolumab followed by adjuvant nivolumab in children and young adults with recurrent or progressive HGG.

SECONDARY OBJECTIVES:

I. To determine the 6 month and 12 month overall survival (OS) in children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab.

II. To determine the 6 month and 12 month progression-free survival (PFS) in children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab.

EXPLORATORY OBJECTIVES:

I. To measure relative changes in interferon gamma associated genetic signature within the tumor microenvironment post administration of neoadjuvant nivolumab in children and young adults with recurrent or progressive HGG compared to archived non-treated recurrent pediatric HGG samples.

II. To explore the correlation of interferon-gamma-associated genetic signature, cell cycle-related genetic signature and infiltrating T lymphocyte (TIL) density and clonality with clinical responses.

III. To measure TIL density post administration of neoadjuvant nivolumab in children and young adults with recurrent or progressive HGG.

IV. To estimate the objective response rate (ORR) in children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab.

V. To evaluate the association between advanced MRI parameters (ADC on DWI, rCBV on dynamic susceptibility contrast (DSC) perfusion MRI, pre-contrast T1 shortening on T1-weighed images, and/or MTRasym on pH-Weighted Amine CEST-EPI) and tumor and peripheral blood immune responses.

VI. To measure relative change in peripheral T-cell response and post administration of neo-adjuvant nivolumab in children and young adults with recurrent or progressive HGG.

VII. To measure PD-1 and PDL-1 expression by immunohistochemistry for children and young adults with recurrent or progressive HGG post neoadjuvant nivolumab and evaluate the differences between the treatment cohort and archived non-treated recurrent pediatric HGG samples.

VIII. To explore the correlation of tumor mutational load with clinical response for children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab.

IX. To assess Quality of Life (QOL) and cognitive measures in children and young adults with recurrent or progressive HGG treated with neoadjuvant nivolumab followed by adjuvant nivolumab.

X. To assess patient and/or proxy satisfaction with study participation via patient-reported outcome (PRO) measures in the context of race ethnicity and other health related social risks.

XI. To assess on therapy toxicity in the context of race, ethnicity and other health related social risks.

OUTLINE: Neoadjuvant nivolumab followed by adjuvant nivolumab evaluation.

NEOADJUVANT TREATMENT: Participants will receive a single infusion of nivolumab of 3 mg/kg 14± 5 days prior to surgery. When scheduling, please keep in mind that the two pre-surgical plasma samples (day of neoadjuvant dose and day of surgery) should be drawn greater than 10 days apart.

Tumor samples will be obtained at time of surgery. The tissue from this surgery (fresh, frozen and FFPE) and the archived tissue (FFPE) from the most recent surgery prior to registration revealing HGG will be processed so as to best achieve the primary, secondary and exploratory objectives.

ADJUVANT TREATMENT: Infusion Cycle #1 should begin as soon as participant has recovered from surgery and has been tapered off of steroids. A maximum dexamethasone dose of 0.1 mg/kg/day is allowed, but preferably have been discontinued (inhaled or topical use of steroids is allowed).

Maintenance Cycle 1+ Day 1 & 15: Participants will receive nivolumab (3mg/kg) IV every 2 weeks until progression or development of unacceptable toxicities or withdrawal. Blood samples will be obtained as pharmacodynamic markers throughout the study (Day 1 of every other cycle). Dose interruptions and symptomatic management will occur based upon preset adverse event determination.

After completion of study treatment, patients are followed up at 30 days and then every 2 months for up to 5 years. ;

Related Conditions & MeSH terms

• Glioblastoma
• Glioma
• Grade III Glioma
• Malignant Glioma
• Recurrence
• Recurrent Glioblastoma
• Recurrent Grade III Glioma
• Recurrent Malignant Glioma

• NCT number: NCT04323046
• Study type: Interventional
• Source: University of California, San Francisco
• Contact: Jannerfer An
• Phone: (415) 476-3831
• Email: PNOC019@ucsf.edu
• Status: Recruiting
• Phase: Phase 1
• Start date: October 2, 2020
• Completion date: March 1, 2029